Leukopenia is a common adverse effect associated with chemotherapy used to treat BC. It has been postulated that the grade of chemotherapy-induced leukopenia (CIL) may be associated with the pharmacokinetics and pharmacodynamics of chemotherapy used in BC and that genetic polymorphism may lead to changes in drug metabolism, efficacy, and adverse events associated with these agents. A recent study examined the role that CIL may play in overall survival (OS) in patients with early BC.
Investigators examined the association between different grades of CIL and survival in patients with early BC who were receiving adjuvant chemotherapy with anthracyclines and taxanes. Patients who were diagnosed with early BC between January 1, 2012, and December 31, 2017, and who had received a full course of chemotherapy were included in this retrospective analysis.
CIL was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 criteria, which categorizes CIL into five grades, with mild being grades 0 to 1, moderate defined as grades 2 to 3, and severe classified as grade 4. The primary endpoint for the study was OS, which referred to the duration from the diagnosis to death from any cause or the final follow-up. Relapse-free survival (RFS) was defined as the period from surgery until the recurrence of local or regional draining lymph nodes or local and regional secondary syngeneic (genetically identical) neoplastic lesions. The researchers also developed a prognostic nomogram for 5- and 8-year OS based on results of univariate and multivariate analyses.
A total of 442 patients were enrolled in the study, with a mean age of 46 years. Almost two-thirds (63.4%) were premenopausal and hormone receptor–positive (HR+). Over two-fifths (41.2%) were human epidermal growth factor receptor 2–positive (HER2+). The majority of BC patients were stage T2 (59.1%). Additionally, 34.0% were N0, 31.9% were N1, 18.3% were N2, and 15.8% were N3. Over three-quarters (76.7%) had a high Ki67 index, defined as >15%. Overall, 71.0% received an anthracycline-taxane regimen, 15.6% received a taxane with an anthracycline +/- cyclophosphamide, and 13.4% received 5-fluorouracil, anthracycline, and cyclophosphamide followed by a taxane.
The investigators found that the development of moderate-to-severe CIL (grades 2-4) was associated with significantly better OS compared with the development of mild CIL (grades 0-1; P = .021). The estimated 5-year OS based on grade was 94.8% for grades 2 to 4 and 83.9% for grades 0 to 1 CIL. While OS was superior in the severe CIL group (compared with the mild CIL group), there was no significant difference in OS between the moderate CIL and the severe CIL group. There was also no difference in RFS between the mild, moderate, or severe CIL groups. Prognostic factors associated with prolonged OS in the moderate and severe CIL groups included premenopausal status, being HER2+, and having N2/N3 or T3-stage disease compared with the mild CIL group. Among those BC patients who were HR+, moderate CIL was associated with shorter OS compared with those who had severe CIL, but there was no difference in OS between those with mild or moderate CIL.
The authors hypothesized that in patients with BC, tumor-associated myeloid cells, which can promote metastasis and colonization growth, may be more suppressed in the presence of severe CIL, thereby having a protective effect. This would need to be demonstrated in a large, well-controlled study. Further, these results are specific to the regimen studied, which contained an anthracycline and taxane and cannot be generalized to other chemotherapeutic regimens used to manage BC.
This study offers preliminary evidence for pharmacists that a possible protective effect may occur if alterations were made in anthracycline-taxane regimens in BC to achieve moderate CIL. However, further study is needed before this is adapted into practice.
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